Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.

ABSTRACT: As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to improve enrichment. The enrichment factor of our blind predictions ranked best among all of the computational submissions, and second best overall. This work represents to our knowledge the first example of the application of an all-atom physics-based binding free energy model to large scale virtual screening. A total of 285 parallel Hamiltonian replica exchange molecular dynamics absolute protein-liga

SUBMITTER: Gallicchio E 

PROVIDER: S-EPMC4137862 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature